供体NK细胞在白血病小鼠半相合骨髓移植中的作用  

The action of donor-derived NK cell in leukemic mice MHC haplotype-mismatched bone marrow transplantation

作　　者：王春燕[1] 谭获[1] 郭坤元[2] 

机构地区：[1]广州医学院第一附属医院肿瘤血液中心,510230 [2]南方医科大学珠江医院血液科

出　　处：《中华血液学杂志》2009年第2期107-110,共4页Chinese Journal of Hematology

基　　金：基金项目：广东省自然科学基金博士科研启动项目（06301119）

摘　　要：目的观察供体NK细胞在白血病小鼠半相合骨髓移植中的作用。方法建立荷EL9611（H-2d）红白血病细胞的CB6F1^H-2b/d小鼠动物模型，5d后随机分为7组，每组10只，移植组在9Gy照射后行C57BL/6^H-2b→CB6F1^H-2b/d骨髓移植。对照组共有5组，对照1组为未治疗组；对照2组为单纯照射组；对照3组为阿糖胞苷治疗组（小鼠腹腔注射阿糖胞苷每只50mg／kg×6d）；对照4组为单纯骨髓细胞移植组（小鼠照射后4h移植C57BIL/6^H-2b小鼠骨髓细胞）；对照5组为移植物抗宿主病（GVHD）对照组（小鼠照射后4h移植C57BL／6^H-2b小鼠骨髓细胞和脾细胞）。实验组共有2组，实验1组：照射后输注C57BL／6^H-2b小鼠NK细胞1×10^6／只，4h后移植C57BL/6^H-2b小鼠骨髓细胞；实验2组：照射后处理同实验1组，4h后移植C57BL／6^H-2b小鼠骨髓细胞和脾细胞。以血象、体重、生存期和病理组织学变化为观察指标并作组间比较。结果对照1、2、3、5组小鼠生存期分别为（10．1±0．9）d、（9．8±0．9）d、（22．7±3．2）d、（20．1±1．7）d，对照4组为（30．1±16．0）d，其中2只小鼠生存期超过30d；实验1、2组生存期分别为（39．1±18．1）d、（49．3±17．2）d，实验1组4只小鼠超过30d，实验2组7只超过30d，其中实验1组同对照1、2、3、5组比较差异均有统计学意义（P〈0．01），实验2组同其他组比较差异均有统计学意义（P〈0．05）。死于白血病的小鼠可见肝脾明显肿大，结构破坏，有大量白血病细胞浸润。实验组长期存活的小鼠出现Y染色体（嵌合率80％～90％）。结论利用荷EL9611（H-2d）红白血病细胞CB6F1^H-2b/d小鼠模型，从C57BL／6^H-2b→CB6F1^H-2b/d方向移植模型上，证明供者NK细胞具有杀灭白血病细胞及降低GVHD的双重作用。Objective To study the role of donor-derived NK cells in haploideatical bone marrow transplantation （BMT） in leukemic mice. Methods CB6F1^H-2b/d mice model of EL9611 （H-2d） erythroleukemia was established by injection of EL9611 （H-2d） cells via tail vein. CB6F1^H-2b/d mice were used as recipient, and C57BL/6^H-2b, mice as donor. Five days later, 70 CB6F1^H-2b/d mice were randomly divided into 7 groups （ 10 mice per group） as follows： group 1 ： without treatment; group 2 ： simple-irradiated group; group 3： treated with cytarabine （Ara-C） at 50 mg/kg × 6 d; group 4： simple BMT; group 5： haploidentical BMT with graft-versus-host disease（GVHD） that injected with bone marrow cells and spleen cells of C57BL/6^H-2b mice 4 hours after irradiation; group 6： after irradiated with 9 Gy, mice were injected with C57BL/6^H-2b NK cells （ 1 × 10^6 ） and 4 hours later with BM cells, group 7 ： after irradiation of 9 Gy, mice were injected with C57 BL/6^H-2b NK cells （ 1 ×10^6） and 4 hours later with BM ceils and spleen ceils. The blood routine test, survival time, body weight, and histopathology in the recipients were observed and compared among these group. Results The survival time was （10. 1 ±0.9）, （9.8±0.9）, （22.7±3.2） and （20.1±1.7） days in groups 1,2,3, and 5 respectively ; was （ 30.1 ±16.0） days in group 4, out of which 2 mice survived for more than 30 days. The survival time was （39.1 ± 18.1 ） and （49.3 ± 17.2） days in groups 6 and 7 respectively, out of which 4 mice in group 6 and 7 mice in group 7 survived for more than 30 days. The survival time in group 6 was much longer than that in group 1,2,3 and 5 （ P 〈 0.01 ）. The survival time in group 7 was much longer than that in other groups （ P 〈 0.05 ）. The liver and spleen enlargement, organ destruction and infiltration with leukemic cells were observed in mice died from leukemia. The chimerism of Y ehromosolne appeared （80% -90% ） in long-term survival miee in groups 6 an

关 键 词：骨髓移植 移植物抗宿主病 杀伤细胞 天然 白血病 实验性 

分 类 号：R686[医药卫生—骨科学]